title: Pharmacological characterization of the vesamicol analogue (+)-[(125)I]MIBT in primate brain.
abstract: The vesamicol analogue, meta-[(125)I]iodobenzyltrozamicol [(+)-[(125)I]MIBT] was evaluated as a probe for the in vitro labeling of the vesicular acetylcholine transporter in primate brain. In the striatum, (+)-[(125)I]MIBT bound a single high-affinity site with a Kd value of 4.4 +/- 0.7 nM. Competition for (+)-[(125)I]MIBT binding to the striatum by a group of vesamicol analogues displayed a pharmacological profile similar to the rank order of potency previously observed for the vesicular acetylcholine transporter on Torpedo synaptic vesicles. High-affinity binding of (+)-[(125)I]MIBT in the occipital cortex was characterized by a Kd value of 4.6 +/- 1.1 nM. However, the rank order of potency for inhibition of (+)-[(125)I]MIBT binding to the occipital cortex by the same test compounds differed from that observed in the striatum. The results suggest that (+)-[(125)I]MIBT is a reliable probe of the vesicular acetylcholine transporter in primate striatum, but its binding in primate occipital cortex is more complex.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, FL 33101, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Staley
authors.forename: D C
authors.initials: DC
authors.lastname: Mash
authors.forename: S M
authors.initials: SM
authors.lastname: Parsons
authors.forename: A B
authors.initials: AB
authors.lastname: Khare
authors.forename: S M
authors.initials: SM
authors.lastname: Efange
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism*; D007462:Iodobenzenes / Q000493:pharmacokinetics; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D026901:Membrane Transport Proteins; D017072:Neostriatum / Q000033:anatomy & histology / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism / Q000493:pharmacokinetics; D011869:Radioligand Assay; D013572:Synaptic Vesicles / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D007462:Iodobenzenes; D008024:Ligands; D026901:Membrane Transport Proteins; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C081671:(3-iodobenzyl)trozamicol; C006189:vesamicol; D000109:Acetylcholine